Immune responses to conventional sub-unit vaccinations to bio-threat agent pathogens has provided only low levels of protective efficacy, and the use of live attenuated vaccines for these pathogens is considered risky. To circumvent these problems, we propose development of adjuvant and delivery systems to enhance the immunogenicity and efficacy of current protocols, and provide a broader spectrum stimulation of the immune system. Using animal and viral chemokine elements and variants, we will examine their properties in DNA vaccination regimens in in vivo models. We will also develop viral delivery systems using attenuated viral vectors to facilitate delivery of antigen/chemokine element combinations. Adjuvants validated in in vivo models will be incorporated into attenuated viral vectors to elicit maximal immune stimulation. Vaccination constructs will be evaluated in murine and rhesus models to ensure safety and efficacy prior to pre-clinical development.